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  1. Article ; Online: Sustained Extracellular Electrical Stimulation Modulates the Permeability of Gap Junctions in

    Stürmer, Sophie / Bolz, Sylvia / Zrenner, Eberhart / Ueffing, Marius / Haq, Wadood

    International journal of molecular sciences

    2024  Volume 25, Issue 3

    Abstract: Neurons build vast gap junction-coupled networks (GJ-nets) that are permeable to ions or small molecules, enabling lateral signaling. Herein, we investigate (1) the effect of blinding diseases on GJ-nets in mouse retinas and (2) the impact of electrical ... ...

    Abstract Neurons build vast gap junction-coupled networks (GJ-nets) that are permeable to ions or small molecules, enabling lateral signaling. Herein, we investigate (1) the effect of blinding diseases on GJ-nets in mouse retinas and (2) the impact of electrical stimulation on GJ permeability. GJ permeability was traced in the acute retinal explants of blind retinal degeneration 1 (
    MeSH term(s) Animals ; Mice ; Retinal Degeneration/therapy ; Retinal Degeneration/pathology ; Retina/pathology ; Gap Junctions ; Electric Stimulation ; Permeability
    Language English
    Publishing date 2024-01-28
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms25031616
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  2. Article: The Noncanonical Role of Complement Factor H in Retinal Pigment Epithelium (RPE) Cells and Implications for Age-Related Macular Degeneration (AMD).

    Armento, Angela / Merle, David Adrian / Ueffing, Marius

    Advances in experimental medicine and biology

    2023  Volume 1415, Page(s) 9–13

    Abstract: Age-related macular degeneration (AMD) is a complex degenerative disease of the retina. Dysfunction of the retinal pigment epithelium (RPE) occurs in early stages of AMD, and progressive RPE atrophy leads to photoreceptor death and visual impairments ... ...

    Abstract Age-related macular degeneration (AMD) is a complex degenerative disease of the retina. Dysfunction of the retinal pigment epithelium (RPE) occurs in early stages of AMD, and progressive RPE atrophy leads to photoreceptor death and visual impairments that ultimately manifest as geographic atrophy (GA), one of the late-stage forms of AMD. AMD is caused by a combination of risk factors including aging, lifestyle choices, and genetic predisposition. A gene variant in the complement factor H gene (CFH) that leads to the Y402H polymorphism in the factor H protein (FH) confers the second highest risk for the development and progression of AMD. FH is a major negative regulator of the alternative pathway of the complement system, and the FH Y402H variant leads to increased complement activation, which is detectable in AMD patients. For this reason, various therapeutic approaches targeting the complement system have been developed, however, so far with very limited or no efficacy. Interestingly, recent studies suggest roles for FH beyond complement regulation. Here, we will discuss the noncanonical functions of FH in RPE cells and highlight the potential implications of those functions for future therapeutic approaches.
    MeSH term(s) Humans ; Complement Factor H/genetics ; Complement Factor H/metabolism ; Retinal Pigment Epithelium ; Macular Degeneration/genetics ; Macular Degeneration/metabolism ; Complement Activation/genetics ; Genetic Predisposition to Disease
    Chemical Substances Complement Factor H (80295-65-4)
    Language English
    Publishing date 2023-07-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 410187-X
    ISSN 0065-2598
    ISSN 0065-2598
    DOI 10.1007/978-3-031-27681-1_2
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    Jg. 1995 - 2021: Lesesall (2.OG)
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  3. Article: Using Micro-Electrode-Array Recordings and Retinal Disease Models to Elucidate Visual Functions: Simultaneous Recording of Local Electroretinograms and Ganglion Cell Action Potentials Reveals the Origin of Retinal Oscillatory Potentials.

    Haq, Wadood / Zrenner, Eberhart / Ueffing, Marius / Paquet-Durand, François

    Bioengineering (Basel, Switzerland)

    2023  Volume 10, Issue 6

    Abstract: Background: The electroretinogram (ERG) is an essential diagnostic tool for visual function, both in clinical and research settings. Here, we establish an advanced in vitro approach to assess cell-type-specific ERG signal components.: Methods: ... ...

    Abstract Background: The electroretinogram (ERG) is an essential diagnostic tool for visual function, both in clinical and research settings. Here, we establish an advanced in vitro approach to assess cell-type-specific ERG signal components.
    Methods: Retinal explant cultures, maintained under entirely controlled conditions, were derived from wild-type mice and
    Results: Scotopic and photopic stimulation discriminated between rod and cone responses in wild-type and mutant retina. The 25 kHz sampling rate allowed the visualization of oscillatory potentials (OPs) in extraordinary detail, revealing temporal correlations between OPs and GC responses. Pharmacological isolation of different retinal circuits found that OPs are generated by inner retinal AC electrical synapses. Importantly, this AC activity helped synchronise GC activity.
    Conclusion: Our µERG protocol simultaneously records the light-dependent activities of the first-, second-, and third-order neurons within the native neuronal circuitry, providing unprecedented insights into retinal physiology and pathophysiology. This method now also enables complete in vitro retinal function testing of therapeutic interventions, providing critical guidance for later in vivo investigations.
    Language English
    Publishing date 2023-06-15
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2746191-9
    ISSN 2306-5354
    ISSN 2306-5354
    DOI 10.3390/bioengineering10060725
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  4. Article ; Online: Therapeutic targeting of the complement system in ocular disease.

    Rathi, Sonika / Hasan, Rafiq / Ueffing, Marius / Clark, Simon J

    Drug discovery today

    2023  Volume 28, Issue 11, Page(s) 103757

    Abstract: The complement system is involved in the pathogenesis of several ocular diseases, providing a rationale for the investigation of complement-targeting therapeutics for these conditions. Dry age-related macular degeneration, as characterised by geographic ... ...

    Abstract The complement system is involved in the pathogenesis of several ocular diseases, providing a rationale for the investigation of complement-targeting therapeutics for these conditions. Dry age-related macular degeneration, as characterised by geographic atrophy (GA), is currently the most active area of research for complement-targeting therapeutics, with a complement C3 inhibitor approved in the United States earlier this year marking the first approved therapy for GA. This review discusses the role of complement in ocular disease, provides an overview of the complement-targeting agents currently under development for ocular conditions, and reflects on the lessons that can be learned from the preclinical investigations and clinical trials conducted in this field to date.
    MeSH term(s) Humans ; Macular Degeneration/drug therapy ; Eye ; Geographic Atrophy/drug therapy ; Geographic Atrophy/etiology ; Geographic Atrophy/pathology
    Language English
    Publishing date 2023-08-30
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1324988-5
    ISSN 1878-5832 ; 1359-6446
    ISSN (online) 1878-5832
    ISSN 1359-6446
    DOI 10.1016/j.drudis.2023.103757
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4725: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
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  5. Book ; Online ; Thesis: Investigation of complement system dependent inflammatory pathways in retinal pigment epithelium (RPE) cells

    Schmidt, Tiziana L. [Verfasser] / Ueffing, Marius [Akademischer Betreuer]

    2023  

    Author's details Tiziana Luisa Schmidt ; Betreuer: Marius Ueffing
    Keywords Medizin, Gesundheit ; Medicine, Health
    Subject code sg610
    Language English
    Publisher Universitätsbibliothek Tübingen
    Publishing place Tübingen
    Document type Book ; Online ; Thesis
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  6. Article ; Online: Pathomechanisms of Inherited Retinal Degeneration and Perspectives for Neuroprotection.

    Tolone, Arianna / Sen, Merve / Chen, Yiyi / Ueffing, Marius / Arango-Gonzalez, Blanca / Paquet-Durand, François

    Cold Spring Harbor perspectives in medicine

    2023  Volume 13, Issue 6

    Abstract: The precise processes causing photoreceptor cell death in retinal degeneration (RD) are still largely unknown but are likely to follow a variety of degenerative mechanisms. While different genetic insults can trigger distinct molecular pathways, ... ...

    Abstract The precise processes causing photoreceptor cell death in retinal degeneration (RD) are still largely unknown but are likely to follow a variety of degenerative mechanisms. While different genetic insults can trigger distinct molecular pathways, eventually these may converge into a limited number of common cell death mechanisms. These mechanisms often involve deregulation of cyclic guanosine monophosphate (cGMP)-signaling and proteostasis, which both may increase photoreceptor energy expenditure. Comprehensive information on these mechanisms may allow for targeted interventions to delay or prevent photoreceptor loss. Here, we review the current knowledge on photoreceptor degenerative mechanisms, focusing on processes triggered by aberrant cGMP-signaling, proteostasis, and energy metabolism. Afterward, we discuss how these pathways could potentially be used to treat photoreceptor degeneration, highlighting data from a number of recent studies on inhibitory cGMP analogs, proteostasis blockers, and interventions aimed at fortifying energetic status. Finally, we provide perspectives on how such experimental approaches could be translated into future clinical applications.
    MeSH term(s) Humans ; Retinal Degeneration/genetics ; Retinal Degeneration/metabolism ; Retina/metabolism ; Neuroprotection ; Photoreceptor Cells/metabolism ; Cell Death
    Language English
    Publishing date 2023-06-01
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2157-1422
    ISSN (online) 2157-1422
    DOI 10.1101/cshperspect.a041310
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  7. Article: Usher syndrome proteins ADGRV1 (USH2C) and CIB2 (USH1J) interact and share a common interactome containing TRiC/CCT-BBS chaperonins.

    Linnert, Joshua / Knapp, Barbara / Güler, Baran E / Boldt, Karsten / Ueffing, Marius / Wolfrum, Uwe

    Frontiers in cell and developmental biology

    2023  Volume 11, Page(s) 1199069

    Abstract: The human Usher syndrome (USH) is the most common form of a sensory hereditary ciliopathy characterized by progressive vision and hearing loss. Mutations in the ... ...

    Abstract The human Usher syndrome (USH) is the most common form of a sensory hereditary ciliopathy characterized by progressive vision and hearing loss. Mutations in the genes
    Language English
    Publishing date 2023-06-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2023.1199069
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  8. Article ; Online: The complement system in age-related macular degeneration.

    Armento, Angela / Ueffing, Marius / Clark, Simon J

    Cellular and molecular life sciences : CMLS

    2021  Volume 78, Issue 10, Page(s) 4487–4505

    Abstract: Age-related macular degeneration (AMD) is a chronic and progressive degenerative disease of the retina, which culminates in blindness and affects mainly the elderly population. AMD pathogenesis and pathophysiology are incredibly complex due to the ... ...

    Abstract Age-related macular degeneration (AMD) is a chronic and progressive degenerative disease of the retina, which culminates in blindness and affects mainly the elderly population. AMD pathogenesis and pathophysiology are incredibly complex due to the structural and cellular complexity of the retina, and the variety of risk factors and molecular mechanisms that contribute to disease onset and progression. AMD is driven by a combination of genetic predisposition, natural ageing changes and lifestyle factors, such as smoking or nutritional intake. The mechanism by which these risk factors interact and converge towards AMD are not fully understood and therefore drug discovery is challenging, where no therapeutic attempt has been fully effective thus far. Genetic and molecular studies have identified the complement system as an important player in AMD. Indeed, many of the genetic risk variants cluster in genes of the alternative pathway of the complement system and complement activation products are elevated in AMD patients. Nevertheless, attempts in treating AMD via complement regulators have not yet been successful, suggesting a level of complexity that could not be predicted only from a genetic point of view. In this review, we will explore the role of complement system in AMD development and in the main molecular and cellular features of AMD, including complement activation itself, inflammation, ECM stability, energy metabolism and oxidative stress.
    MeSH term(s) Aging ; Animals ; Complement Activation ; Complement System Proteins/metabolism ; Genetic Predisposition to Disease ; Humans ; Inflammation/physiopathology ; Macular Degeneration/immunology ; Macular Degeneration/metabolism ; Macular Degeneration/pathology ; Oxidative Stress ; Risk Factors
    Chemical Substances Complement System Proteins (9007-36-7)
    Language English
    Publishing date 2021-03-09
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-021-03796-9
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 195: Show issues Location:
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  9. Article: Method for siRNA delivery in retina explants.

    Bassetto, Marco / Sen, Merve / Poulhes, Florent / Arango-Gonzalez, Blanca / Ueffing, Marius / Zelphati, Olivier

    Methods in cell biology

    2023  Volume 176, Page(s) 199–216

    Abstract: Several barriers prevent the delivery of nucleic acids to the retina and limit the application of established technologies, such as RNA interference (RNAi), in the study of retinae biology. Organotypic culture of retinal explants is a convenient method ... ...

    Abstract Several barriers prevent the delivery of nucleic acids to the retina and limit the application of established technologies, such as RNA interference (RNAi), in the study of retinae biology. Organotypic culture of retinal explants is a convenient method to decrease the complexity of the biological environment surrounding the retina while preserving most of its physiological features. Nevertheless, eliciting significant, non-toxic RNAi in retina explants is not straightforward. Retina explants are mainly constituted by neurons organized in discrete circuits embedded within a complex 3D extracellular matrix. About 70% of these neurons are post-mitotic ciliated cells that respond to light. Unfortunately, like the other cells of the retina, photoreceptors are refractory to transfection, and a toxic delivery of nucleic acid often results in permanent cell loss. RNAi has been applied to retina explants using electroporation, viral, and non-viral vectors but with reproducible, poor gene silencing efficiency. In addition, only a few superficial cells can be transduced/transfected in adult retina explants. Therefore, viruses are often injected into the eye of embryos prior to excision of the retina. However, embryonic explants are not the best model to study most retina diseases since even if they are viable for several weeks, the pathological phenotype often appears later in development. We describe a robust and straightforward method to elicit significant RNAi in adult retina explant using Reverse Magnetofection. This transfection method offers a simple tool for non-toxic gene knockdown of specific genes in adult retina explants by using cationic magnetic nanoparticles (MNPs) to complex and deliver short interfering-RNAs (siRNA) in retina cells under the action of a magnetic field.
    MeSH term(s) RNA, Small Interfering/genetics ; Retina ; Transfection ; RNA Interference ; Electroporation
    Chemical Substances RNA, Small Interfering
    Language English
    Publishing date 2023-04-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 0091-679X
    ISSN 0091-679X
    DOI 10.1016/bs.mcb.2022.12.017
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  10. Article ; Online: Human CRB1 and CRB2 form homo- and heteromeric protein complexes in the retina.

    Stehle, Isabel F / Imventarza, Joel A / Woerz, Franziska / Hoffmann, Felix / Boldt, Karsten / Beyer, Tina / Quinn, Peter Mj / Ueffing, Marius

    Life science alliance

    2024  Volume 7, Issue 6

    Abstract: Crumbs homolog ... ...

    Abstract Crumbs homolog 1
    MeSH term(s) Animals ; Humans ; Zebrafish/genetics ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Retina/metabolism ; Retinitis Pigmentosa/genetics ; Retinitis Pigmentosa/metabolism ; Leber Congenital Amaurosis/genetics ; Leber Congenital Amaurosis/metabolism ; Eye Proteins/genetics ; Eye Proteins/metabolism ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Carrier Proteins/metabolism
    Chemical Substances Membrane Proteins ; CRB1 protein, human ; Eye Proteins ; Nerve Tissue Proteins ; CRB2 protein, human ; Carrier Proteins
    Language English
    Publishing date 2024-04-03
    Publishing country United States
    Document type Journal Article
    ISSN 2575-1077
    ISSN (online) 2575-1077
    DOI 10.26508/lsa.202302440
    Database MEDical Literature Analysis and Retrieval System OnLINE

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